Factors modulating the response of a porcine renal tubular cell line to calcitonin and antidiuretic hormone.

A cell line (LLC-PK1) isolated from porcine kidney increases 3'5'-cyclic adenosine monophosphate (cAMP) content when incubated with salmon calcitonin (SCT) or antidiuretic hormone (ADH). We have examined several factors which modulate the hormone-induced changes in cAMP levels in these cells. Preincubation with increasing concentrations of SCT results in a dose-dependent decrease in cAMP levels in cells retested with this hormone. Addition of 3-isobutyl-l-methylxanthine (IBMX) to cells preincubated with SCT results in 15--30-fold increases in cAMP levels compared to cells preincubated without this hormone. These observations suggest that the decrease in SCT-induced cAMP response in cells pretreated with this hormone is related at least in part to stimulation of phosphodiesterase activity. Preincubation with ADH does not affect subsequent cAMP response to either ADH or SCT, suggesting that these hormones interact with different cell surface receptors. Cell cycle and plating density also affect cAMP levels. cAMP content per cell increases with increasing cell density, which is associated with an increase in the SCT-induced cAMP response. These studies illustrate that factors other than receptor occupancy modulate cAMP responses of these cells to specific hormones.